PROJECT SUMMARY/ABSTRACT - OVERALL We propose to establish a Center of Biomedical Research Excellence (COBRE) in Pharmaceutical Research and Innovation at the University of Kentucky (UK). CPRI will serve as a comprehensive multidisciplinary center focused on translational chemical biology [the nexus of chemical biology (the application of chemical biology principles to develop validated probe/models to advance our understanding of biology) and pharmaceutical science (the application of pharmaceutical principles to advance leads/materials/devices that address unmet clinical needs)]. The COBRE will leverage and develop unique translational chemical biology research support infrastructure/expertise to facilitate junior faculty mentorship and career development, innovative biomedical research probe/tool/model/materials development and validation, and the early advancement of potential ?translatable? assets. Key COBRE infrastructure to be developed and implemented in Phase I includes the CPRI Administrative Core and two research support cores (the Translational Core and the Computational Core) and the COBRE will also further develop and leverage the COBRE for Molecular Medicine?s Organic Synthesis Core to support CPRI junior faculty projects/pilots. CPRI will initially support four outstanding junior investigators working in three therapeutic areas (cancer, infectious disease and cardiovascular disease). Our overarching hypothesis is that CPRI?s translational chemical biology focus presents a distinctly unique UK platform to: i) engage, integrate and mentor junior faculty from a broad range of fundamental, applied and clinical disciplines; ii) facilitate the development of new impactful probes/tools/models and advance innovative transdisciplinary research; and iii) bridge the gap between basic academic research discoveries and commercial/clinical application via education, mentorship and key support infrastructure. CPRI?s distinct focus on translational chemical biology and early translation fills a notable preclinical research gap for many of UK?s exceptional research centers strategically focused on understanding, treating and preventing the major diseases that contribute to Kentucky?s disproportionate health challenges. Anticipated COBRE outcomes include an increase in the number and diversity of UK junior faculty engaged in translational chemical biology research and better-prepared to develop and employ innovative biomedical probes/tools/models/materials, new sustainable UK translational chemical biology research support infrastructure and capabilities, an increase in the number of UK junior faculty with independent research funding, and a boost in the number potentially ?translatable? UK preclinical assets.